Fetal Lungs Protein Release Triggers Labor to Begin

Babies know when and how to be born.
Each one knows when s/he is ready for life on the outside.
Let's not rush them.
Let's trust them.

We've long known that a mammal's lungs are the last organ to develop inutero before it is baby's time to exit. Disrupting this normal process (and initiating/inducing labor to start before a baby triggers labor on his/her own) frequently causes a cascade of complications - from difficulty in latch, poor breathing, increased infection, decreased immunity, under development, failure to thrive, and an increase in SIDS.

Drs. Carole Mendelson, Jennifer Condon and Pancharatnam Jeyasuria published findings that a substance secreted by the lungs of a developing fetus contains the key signal that initiates labor.

The protein released from the lungs of a developing mouse fetus initiates a cascade of chemical events leading to the mother's initiation of labor. This research, which has implications for humans, marks the first time a link between a specific fetal lung protein and labor has been identified, said Mendelson, professor of BioChemistry and Obstetrics and Gynecology and senior author of the study. Their research appears in the Proceedings of the National Academy of Sciences and is currently available online here.

The initiation of term labor is carefully timed to begin only after the embryo is sufficiently mature to survive outside the womb. Previous studies suggested that the signal for labor in humans may arise from the fetus, but the nature of the signal and actual mechanism was unclear. In this study, researchers found that the key labor triggering substance, surfactant, is essential for normal breathing outside the womb.

"We found that a protein within lung, surfactant, serves as a hormone of labor that signals to the mother's uterus when the fetal lungs are sufficiently mature to withstand the critical transition from life in fluid to airbreathing," said Mendelson.

"No one really understands what causes normal or preterm labor. There may be several chemical pathways that lead to labor, but we think that this surfactant protein, which is also produced by the fetal lung in humans, may be the first hormonal signal for labor to begin," reported Mendelson, who is also co-director of the North Texas March of Dimes Birth Defects Center at UT Southwestern.

In humans the signaling protein, called surfactant protein A, or SP-A, also helps immune cells, called macrophages, fight off infections in the lungs of children and adults by gobbling up bacteria, viruses and fungi that infiltrate the lung airway.

"Women who go into preterm labor frequently have an infection of the membranes that surround the fetus, and the number of macrophages in the wall of the uterus increases with the initiation of preterm labor. When women go into labor in their own time, at term, they also have an increase in macrophages in the uterus," Mendelson said.

This led the researchers to investigate whether there was a connection between what happens during normal labor at term and in infected mothers who go into early labor.

Mendelson continued, "This also raised the question: If bacterial infection can cause increased macrophage infiltration of the uterus in preterm labor, what is the signal for the enhanced macrophage migration to the uterus at term?"

In mice, the developing fetal lung starts producing SP-A at 17 days gestation; full-term delivery occurs at 19 days. The developing human fetus starts producing SP-A in increasing amounts after 32 weeks of a 40+week normal gestation, at which time the baby's lungs are essentially developed. As the fetus "breathes" amniotic fluid in the womb, the protein is released into the fluid.

"The SP-A protein binds to macrophages in the amniotic fluid, macrophages that come from the fetus itself," said Dr. Jennifer Condon, a postdoctoral researcher in BioChemistry and the study's lead author.

The macrophages, activated by the protein, make their way through the amniotic fluid to the wall of the uterus. Once embedded there, they produce a chemical that stimulates an inflammatory response in the uterus, ultimately leading to labor.

Researchers also found that injecting a pregnant mouse with SP-A before day 17 of the pregnancy caused the mouse to deliver early. Injection of pregnant mice with an antibody that blocks SP-A function caused them to deliver late. This would cause us to believe that women who carry babies post 42 weeks (as is common in some family lines) may do so because the necessary SP-A function is happening at later date in gestation (starting at 34 weeks instead of 32 weeks, for example).

Identifying the receptors on the macrophages to which the SP-A protein binds will be the next step, Mendelson said. "We think that bacteria may be binding to the same receptor on the macrophages to cause preterm labor in women. The bacteria mimic the function of SP-A, initiating the chemical reactions that lead to premature labor. If we knew more about this receptor on amniotic fluid macrophages, we may be able to design therapies or inhibitors to block preterm labor."

Other researchers participating in the study were Dr. Pancharatnam Jeyasuria, a research fellow in internal medicine and former fellow Julie Faust, now a medical student at Texas A&M University.

24 comments:

I have heard of this before and it still makes sense. It also makes sense that a woman with preterm labor may have this begin earlier in their pregnancy. Especially women like me who have disorders that cause hormone differences! My children have all been born between 36 and 37 weeks with perfectly healthy lungs. I have been in labor but "assisted" with pitocin when labor stalled (never again!!).. but the labor itself started naturally. All 6 children have been born with perfectly healthy lungs with NO problems or health issues. It just seems to be that my children don't "need" 40 weeks! LOL... As I said, perhaps the release of the SP-A starts a bit earlier for some women?

Interesting. My labor with baby #4 started with a spontaneous ROM at home at 36 weeks, 6 days. Labor and delivery were uneventful. However baby's lungs weren't at all ready--persistent pulmonary hypertension of the neonate, along with a touch of hyaline membrane disease. So, in this case, I can't believe that fetal lung development triggered his labor; but then again, we know that labor does occur before babies are ready to survive outside the womb as well.

Makes me re-think the shots my old OB gave me to help my Baby's lungs develop, when I was having preterm contractions at 24 weeks. Seems like that would only make my early labor progress instead of stopping.

Yes, the shots are to develop surfactant in the lungs in case of premature delivery. I think "Stay at Home Momma of 1 and Counting" understands that. She's saying that maybe rushing the surfactant to develop in the lungs would make the labor happen early, not the steroid shots themselves would make labor start prematurely. I've had 2 babies, both premature and I got those shots, but I had different situations with each. My first baby, I started having contractions spontaneously (with no amniotic fluid leaking) at 31 weeks/6 days. My labor was slowed, but not stopped with drugs such as magnesium sulfate and others. At 31 weeks/6 days and 32 weeks/0 days, I received the 2-steroid shot series, 24 hours apart for each shot. My labor was barely evident until my water broke with no warning at 32 weeks/2 days. I gave birth at 32 weeks/3 days. With my 2nd baby, I was doing the weekly intramuscular 17p shots (alpha hydroxy progesterone) that are recommended by The March of Dimes for those who've had a previous preterm singleton premature birth for no known reason. They relax the uterus to prevent contractions from starting early. But with this one, my contractions didn't start early. My water spontaneously broke, without warning, less than 24 hours after I had received the final one of my two steroid shots to mature the baby's lungs. I did go a little longer with my 2nd baby. He was born at 34 weeks/1 day, so I think the 17p did help. First baby was 4 lb. 4 oz., 2nd was 5 lb. 2 oz., so the extra time gave my 2nd time to be a healthier birth weight. But, this article makes me wonder what would have happened if I hadn't gotten those steroid shots when I was pregnant with my 2nd baby. I wonder if the surfactant that they caused to develop signaled my water to break. I would think that it would take more than 24 hours for the surfactant to increase enough to tell my body to go into labor. I think this needs to be looked into a lot more. My OB didn't want to give me the steroid shots before 33 weeks/6 days. Now, I'm wondering if she knew something about surfactant signaling labor that she didn't want to tell me. If I had it to do all over again, I might have waited and got the steroid shots only IF I went into labor early, not BEFORE I went into labor early.

Seems like an awful lot of tampering and speculation.My daughter had mild contractions throughout her last trimester on and off, she was not alarmed. She found out it was normal, it was warm up. They never became very regular til she went into term labor 42 weeks plus.

When I asked my OB what was the "Official" cause of initiation of term labor, she informed that that it is still to this day largely unknown. It is nice to have a glimpse into what may be the cause of such a seemingly spontaneous event. Maybe it is as simple as uterine inflammation. I was always under the assumption that the release of Oxytocin was the chemical/hormonal culprit.

I had preterm contractions at 28 weeks and I was given the shot to help the baby's lung to develope just in case the contractions continued. Had to be put on bed for three days in the hospotal and was at home as well. Do you think its okay? Please anyone

Anon - the drugs given to help baby's lungs develop more rapidly are to ensure a better chance at survival if preterm birth occurs. Sounds like you are in good hands. Much love to you and your little one.

I ended up with a medical induction at 42 weeks and 1 day. I didn't feel like it would be safe to go much longer than that, in case the placenta was starting to deteriorate. Little guy was healthy and ready... I guess his lungs just didn't want to release that hormone! It took a lot of stubbornness on my part to get my doctor to let me go that long. Apparently she normally induces at 39w. Next baby will be with a different doctor.

'Placental deterioration' is one of those things physicians often use to scare women into inductions. 42 weeks is AVERAGE -- not the end cut off. My son was born at 44 weeks, and I know many others who have gone post-42 as well. Of course, these are just more case examples, but averages tell us that the placenta does not magically breakdown or stop doing its job at 42 weeks. ;) This physician should *never* be inducing at 39 weeks -- there could be many babies whose dates are off by as much as 2 weeks, which would cause them to be prematurely born at 37. :/

I heard many years ago that when the baby's lungs were ready to breathe air, a gas was produced that caused a burp. As it passed into the amionic fluid it caused the placenta to break, initiating the first stage of labor.

This is fascinating! One of my children was born prematurely and passed, two were born preterm while my finial child wanted to stay forever; at least that’s how it felt. I’m interested to see what happens next in this research regarding the correlation between the lung development and the initiation of labor. It’s a great leap in the right direction and very encouraging to hear so much positivity in regards to more ways to possibly help the body in responding to the hormonal triggers. The possibility of being able to not only encourage lung maturation in cases where it’s likely a child won’t come to term but maybe being able to communicate with the body by introducing synthetic triggers mimicking the natural ones to override the body’s desire to initiate labor before it’s safe to do so will be amazing. Any research that will find safe viable solutions that will in time save families the devastation of losing a child.